Abbasnezhad A, Hayatdavoudi P, Niazmand
S, Mahmoudabady M. 2015. The effects
of hydroalcoholic extract of Nigella sativa
seed on oxidative stress in hippocampus
of STZ-induced diabetic rats. Avicenna J
Phytomed, 5: 333-340.
Al-Naqeeb G, Ismail M. 2009. Regulation of
apolipoprotein A-1 and apolipoprotein
B100 genes by thymoquinone rich
fraction and thymoquinone in HEPG2
cells. J Food Lipids, 16: 245-258.
Amizadeh S, Rashtchizadeh N, Khabbazi A,
Ghorbanihaghjo A, Ebrahimi AA,
Vatankhah AM, Malek Mahdavi A,
Taghizadeh M. 2020. Effect of Nigella
sativa oil extracts on inflammatory and
oxidative stress markers in Behcet's
disease: A randomized, double-blind,
placebo-controlled clinical trial. Avicenna
J Phytomed, 10: 181-189.
Argo CK, Northup PG, Al-Osaimi AM,
Caldwell SH. 2009. Systematic review of
risk factors for fibrosis progression in
non-alcoholic steatohepatitis. J Hepatol,
51: 371-379.
Asgharzadeh F, Bargi R, Beheshti F, Hosseini
M, Farzadnia M, Khazaei M. 2017.
Thymoquinone restores liver fibrosis and
improves oxidative stress status in a
lipopolysaccharide-induced inflammation
model in rats. Avicenna J Phytomed, 7:
502-510.
Bai T, Yang Y, Wu YL, Jiang S, Lee JJ, Lian
LH, Nan JX. 2014. Thymoquinone
alleviates thioacetamide-induced hepatic
fibrosis and inflammation by activating
LKB1-AMPK signaling pathway in mice.
Int Immunopharmacol, 19: 351-357.
Balbaa M, Abdulmalek SA, Khalil S. 2017.
Oxidative stress and expression of insulin
signaling proteins in the brain of diabetic
rats: Role of Nigella sativa oil and
antidiabetic drugs. PLoS One, 12:
e0172429.
Ben El Mostafa S, Abdellatif M. 2020. Herbal
Medicine in Chronic Diseases Treatment:
Determinants, Benefits and Risks. pp. 85-
95.
Benhaddou-Andaloussi A, Martineau L,
Vuong T, Meddah B, Madiraju P, Settaf
A, Haddad PS. 2011. The in vivo
antidiabetic activity of Nigella sativa is
mediated through activation of the AMPK
pathway and increased muscle Glut4
Content. Evid Based Complement
Alternat Med, 2011: 538671.
Biddinger SB, Hernandez-Ono A, RaskMadsen C, Haas JT, Aleman JO, Suzuki
R, Scapa EF, Agarwal C, Carey MC,
Stephanopoulos G, Cohen DE, King GL,
Ginsberg HN, Kahn CR. 2008. Hepatic
insulin resistance is sufficient to produce
dyslipidemia and susceptibility to
atherosclerosis. Cell Metab, 7: 125-134.
Mohtashamian et al.
AJP, Vol. 13, No. 1, Jan-Feb 2023 30
Brufau G, Canela MA, Rafecas M. 2008.
Phytosterols: physiologic and metabolic
aspects related to cholesterol-lowering
properties. Nutr Res, 28: 217-225.
Catena C, Bernardi S, Sabato N, Grillo A,
Ermani M, Sechi LA, Fabris B, Carretta
R, Fallo F. 2013. Ambulatory arterial
stiffness indices and non-alcoholic fatty
liver disease in essential hypertension.
Nutr Metab Cardiovasc Dis, 23: 389-393.
Chartampilas E. 2018. Imaging of
nonalcoholic fatty liver disease and its
clinical utility. Hormones (Athens), 17:
69-81.
Chen Z, Wang L, Yang G, Xu H, Liu J. 2015.
Chinese herbal medicine combined with
conventional therapy for blood pressure
variability in hypertension patients: a
systematic review of randomized
controlled trials. Evid Based Complement
Alternat Med, 2015: 582751.
Cicero AF, De Sando V, Izzo R, Vasta A,
Trimarco A, Borghi C. 2012. Effect of a
combined nutraceutical containing
Orthosiphon stamineus effect on blood
pressure and metabolic syndrome
components in hypertensive
dyslipidaemic patients: a randomized
clinical trial. Complement Ther Clin
Pract, 18: 190-194.
Cicero AFG, Colletti A, Bellentani S. 2018.
Nutraceutical approach to non-alcoholic
fatty liver disease (NAFLD): The
available clinical evidence. Nutrients, 10:
1153.
Darakhshan S, Bidmeshki Pour A,
Hosseinzadeh Colagar A, Sisakhtnezhad
S. 2015. Thymoquinone and its
therapeutic potentials. Pharmacol Res, 95-
96: 138-158.
Darand M, Darabi Z, Yari Z, Hedayati M,
Shahrbaf MA, Khoncheh A, HosseiniAhangar B, Alavian SM, Hekmatdoost A.
2019a. The effects of black seed
supplementation on cardiovascular risk
factors in patients with nonalcoholic fatty
liver disease: A randomized, doubleblind, placebo-controlled clinical trial.
Phytother Res, 33: 2369-2377.
Darand M, Darabi Z, Yari Z, Saadati S,
Hedayati M, Khoncheh A, HosseiniAhangar B, Alavian SM, Hekmatdoost A.
2019b. Nigella sativa and inflammatory
biomarkers in patients with non-alcoholic
fatty liver disease: Results from a
randomized, double-blind, placebocontrolled, clinical trial. Complement
Ther Med, 44: 204-209.
Dowman JK, Tomlinson JW, Newsome PN.
2011. Systematic review: the diagnosis
and staging of non-alcoholic fatty liver
disease and non-alcoholic steatohepatitis.
Aliment Pharmacol Ther, 33: 525-540.
Fallo F, Dalla Pozza A, Sonino N, Federspil G,
Ermani M, Baroselli S, Catena C, Soardo
G, Carretta R, Belgrado D, Fabris B,
Sechi LA. 2008. Nonalcoholic fatty liver
disease, adiponectin and insulin resistance
in dipper and nondipper essential
hypertensive patients. J Hypertens, 26:
2191-2197.
Gandhi CR. 2017. Hepatic stellate cell
activation and pro-fibrogenic signals. J
Hepatol, 67: 1104-1105.
Goyal SN, Prajapati CP, Gore PR, Patil CR,
Mahajan UB, Sharma C, Talla SP, Ojha S
K. 2017. Therapeutic potential and
pharmaceutical development of
thymoquinone: A multitargeted molecule
of natural origin. Front Pharmacol, 8: 656.
Hadi V, Kheirouri S, Alizadeh M, Khabbazi
A, Hosseini H. 2016. Effects of Nigella
sativa oil extract on inflammatory
cytokine response and oxidative stress
status in patients with rheumatoid
arthritis: a randomized, double-blind,
placebo-controlled clinical trial. Avicenna
J Phytomed, 6: 34-43.
Hamaguchi M, Kojima T, Takeda N,
Nakagawa T, Taniguchi H, Fujii K,
Omatsu T, Nakajima T, Sarui H,
Shimazaki M, Kato T, Okuda J, Ida K.
2005. The metabolic syndrome as a
predictor of nonalcoholic fatty liver
disease. Ann Intern Med, 143: 722-728.
Hasani-Ranjbar S, Nayebi N, Larijani B,
Abdollahi M. 2009. A systematic review
of the efficacy and safety of herbal
medicines used in the treatment of
obesity. World J Gastroenterol: WJG, 15:
3073-3085.
Hasani-Ranjbar S, Nayebi N, Moradi L, Mehri
A, Larijani B, Abdollahi M. 2010. The
efficacy and safety of herbal medicines
used in the treatment of hyperlipidemia; a
systematic review. Curr Pharm Des, 16:
2935-2947.
Hashempur MH, Heydari M, Mosavat S H,
Heydari ST, Shams M. 2015.
Complementary and alternative medicine
Nigella Sativa supplementation and NAFLD
AJP, Vol. 13, No. 1, Jan-Feb 2023 31
use in Iranian patients with diabetes
mellitus. J Integr Med, 13: 319-325.
Higgins JP, Thompson SG, Deeks JJ, Altman
DG. 2003. Measuring inconsistency in
meta-analyses. Bmj, 327: 557-560.
Hosseini B, Saedisomeolia A, Wood LG,
Yaseri M, Tavasoli S. 2016. Effects of
pomegranate extract supplementation on
inflammation in overweight and obese
individuals: A randomized controlled
clinical trial. Complement Ther Clin
Pract, 22: 44-50.
Hosseini S, Razmgah G, Nematy M, Esmaily
H, Yousefi M, Kamalinejad M, Mosavat
SH. 2018. Efficacy of black seed (Nigella
sativa) and lemon balm (Melissa
officinalis) on non-alcoholic fatty liver
disease: A randomized controlled clinical
trial. Iran Red Crescent Med J, 20:
e59183.
Hosseinian S, Hadjzadeh MA, Roshan NM,
Khazaei M, Shahraki S, Mohebbati R,
Rad AK. 2018. Renoprotective effect of
Nigella sativa against cisplatin-induced
nephrotoxicity and oxidative stress in rat.
Saudi J Kidney Dis Transpl, 29: 19-29.
Hrebicek J, Janout V, Malincikova J,
Horakova D, Cizek L. 2002. Detection of
insulin resistance by simple quantitative
insulin sensitivity check index QUICKI
for epidemiological assessment and
prevention. J Clin Endocrinol Metab, 87:
144-147.
Hussain M, Tunio AG, Akhtar L, Shaikh GS.
2017. Effects of nigella sativa on various
parameters in Patients of non-alcoholic
fatty liver disease. J Ayub Med Coll
Abbottabad, 29: 403-407.
Katsiki N, Mikhailidis DP, Mantzoros CS.
2016. Non-alcoholic fatty liver disease
and dyslipidemia: An update.
Metabolism, 65: 1109-1123.
Keating SE, Hackett DA, George J, Johnson N
A. 2012. Exercise and non-alcoholic fatty
liver disease: a systematic review and
meta-analysis. J Hepatol, 57: 157-166.
Khaldi T, Chekchaki N, Boumendjel M, Taibi
F, Abdellaoui M, Messarah M,
Boumendjel A. 2018. Ameliorating
effects of Nigella sativa oil on
aggravation of inflammation, oxidative
stress and cytotoxicity induced by
smokeless tobacco extract in an allergic
asthma model in Wistar rats. Allergol
Immunopathol (Madr), 46: 472-481.
Khonche A, Huseini H F, Gholamian M,
Mohtashami R, Nabati F, Kianbakht S.
2019. Standardized Nigella sativa seed oil
ameliorates hepatic steatosis,
aminotransferase and lipid levels in nonalcoholic fatty liver disease: A
randomized, double-blind and placebocontrolled clinical trial. J
Ethnopharmacol, 234: 106-111.
Lindenmeyer CC, McCullough AJ. 2018. The
natural history of nonalcoholic fatty liver
disease-an evolving view. Clin Liver Dis,
22: 11-21.
Lomonaco R, Ortiz-Lopez C, Orsak B, Webb
A, Hardies J, Darland C, Finch J,
Gastaldelli A, Harrison S, Tio F, Cusi K.
2012. Effect of adipose tissue insulin
resistance on metabolic parameters and
liver histology in obese patients with
nonalcoholic fatty liver disease.
Hepatology, 55: 1389-1397.
Lopez-Suarez A, Guerrero JM, ElviraGonzalez J, Beltran-Robles M, CanasHormigo F, Bascunana-Quirell A. 2011.
Nonalcoholic fatty liver disease is
associated with blood pressure in
hypertensive and nonhypertensive
individuals from the general population
with normal levels of alanine
aminotransferase. Eur J Gastroenterol
Hepatol, 23: 1011-1017.
Lupidi G, Camaioni E, Khalifé H, Avenali L,
Damiani E, Tanfani F, Scirè A. 2012.
Characterization of thymoquinone
binding to human α₁-acid glycoprotein. J
Pharm Sci, 101: 2564-2573.
Mariod AA, Ibrahim RM, Ismail M, Ismail N.
2009. Antioxidant activity and phenolic
content of phenolic rich fractions obtained
from black cumin (Nigella sativa)
seedcake. Food Chemistry, 116: 306-312.
Mokhtari Z, Gibson DL, Hekmatdoost A.
2017. Nonalcoholic fatty liver disease, the
gut microbiome, and diet. Adv Nutr, 8:
240-252.
Moschen AR, Wieser V, Tilg H. 2012.
Adiponectin: Key player in the adipose
tissue-liver crosstalk. Curr Med Chem,
19: 5467-5473.
Mummadi RR, Kasturi KS, Chennareddygari
S, Sood GK. 2008. Effect of bariatric
surgery on nonalcoholic fatty liver
disease: systematic review and metaanalysis. Clin Gastroenterol Hepatol, 6:
1396-1402.
Mohtashamian et al.
AJP, Vol. 13, No. 1, Jan-Feb 2023 32
Muneera KE, Majeed A, Naveed AK. 2015.
Comparative evaluation of Nigella sativa
(Kalonji) and simvastatin for the
treatment of hyperlipidemia and in the
induction of hepatotoxicity. Pak J Pharm
Sci, 28: 493-498.
Pagano G, Pacini G, Musso G, Gambino R,
Mecca F, Depetris N, Cassader M, David
E, Cavallo-Perin P, Rizzetto M. 2002.
Nonalcoholic steatohepatitis, insulin
resistance, and metabolic syndrome:
further evidence for an etiologic
association. Hepatology, 35: 367-372.
Promrat K, Kleiner DE, Niemeier HM,
Jackvony E, Kearns M, Wands JR, Fava J
L, Wing RR. 2010. Randomized
controlled trial testing the effects of
weight loss on nonalcoholic
steatohepatitis. Hepatology, 51: 121-129.
Rashidmayvan M, Mohammadshahi M,
Seyedian SS, Haghighizadeh MH. 2019.
The effect of Nigella sativa oil on serum
levels of inflammatory markers, liver
enzymes, lipid profile, insulin and fasting
blood sugar in patients with non-alcoholic
fatty liver. J Diabetes Metab Disord, 18:
453-459.
Sahebkar A, Soranna D, Liu X, Thomopoulos
C, Simental-Mendia LE, Derosa G,
Maffioli P, Parati G. 2016. A systematic
review and meta-analysis of randomized
controlled trials investigating the effects
of supplementation with Nigella sativa
(black seed) on blood pressure. J
Hypertens, 34: 2127-2135.
Saleh HA, Abu-Rashed AH. 2007. Liver
biopsy remains the gold standard for
evaluation of chronic hepatitis and
fibrosis. J Gastrointestin Liver Dis, 16:
425-426.
Salehi B, Quispe C, Imran M, Ul-Haq I,
Živković J, Abu-Reidah IM, Sen S,
Taheri Y, Acharya K, Azadi H, Del Mar
Contreras M, Segura-Carretero A,
Mnayer D, Sethi G, Martorell M, Abdull
Razis AF, Sunusi U, Kamal RM, Rasul
Suleria HA, Sharifi-Rad J. 2021. Nigella
plants - traditional uses, bioactive
phytoconstituents, preclinical and clinical
studies. Front Pharmacol, 12: 625386.
Salem ML. 2005. Immunomodulatory and
therapeutic properties of the Nigella
sativa L. seed. Int Immunopharmacol, 5:
1749-1770.
Salgado AL, Carvalho L, Oliveira AC, Santos
VN, Vieira JG, Parise ER. 2010. Insulin
resistance index (HOMA-IR) in the
differentiation of patients with nonalcoholic fatty liver disease and healthy
individuals. Arq Gastroenterol, 47: 165-
169.
Samani NB, Jokar A, Soveid M, Heydari M,
Mosavat SH. 2016. Efficacy of the
hydroalcoholic extract of Tribulus
terrestris on the serum glucose and lipid
profile of women with diabetes mellitus:
A double-blind randomized placebocontrolled clinical trial. J Evid Based
Complementary Altern Med, 21: Np91-7.
Sayed-Ahmed MM, Nagi MN. 2007.
Thymoquinone supplementation prevents
the development of gentamicin-induced
acute renal toxicity in rats. Clin Exp
Pharmacol Physiol, 34: 399-405.
Sayiner M, Lam B, Golabi P, Younossi ZM.
2018. Advances and challenges in the
management of advanced fibrosis in
nonalcoholic steatohepatitis. Therap Adv
Gastroenterol, 11: 1756284818811508.
Sharifi N, Amani R. 2019. Vitamin D
supplementation and non-alcoholic fatty
liver disease: A critical and systematic
review of clinical trials. Crit Rev Food
Sci Nutr, 59: 693-703.
Sharifi N, Amani R, Hajiani E, Cheraghian B.
2014. Does vitamin D improve liver
enzymes, oxidative stress, and
inflammatory biomarkers in adults with
non-alcoholic fatty liver disease? A
randomized clinical trial. Endocrine, 47:
70-80.
Sheashea M, Xiao J, Farag MA. 2021. MUFA
in metabolic syndrome and associated risk
factors: is MUFA the opposite side of the
PUFA coin? Food Funct, 12: 12221-
12234.
Silva Figueiredo P, Inada AC, Ribeiro
Fernandes M, Granja Arakaki D, Freitas
KC, Avellaneda Guimaraes RC, Aragao
do Nascimento V, Aiko Hiane P. 2018.
An overview of novel dietary
supplements and food ingredients in
patients with metabolic syndrome and
non-alcoholic fatty liver disease.
Molecules, 23: 877.
Sterne JAC, Savović J, Page MJ, Elbers RG,
Blencowe NS, Boutron I, Cates CJ,
Cheng HY, Corbett MS, Eldridge SM,
Emberson JR, Hernán MA, Hopewell S,
Hróbjartsson A, Junqueira DR, Jüni P,
Nigella Sativa supplementation and NAFLD
AJP, Vol. 13, No. 1, Jan-Feb 2023 33
Kirkham JJ, Lasserson T, Li T,
McAleenan A, Reeves BC, Shepperd S,
Shrier I, Stewart LA, Tilling K, White IR,
Whiting PF, Higgins JPT. 2019. RoB 2: a
revised tool for assessing risk of bias in
randomised trials. Bmj, 366: l4898.
Sui Y, Zhao H, Wong V, Brown N, Li X,
Kwan A, Hui H, Ziea E, Chan J. 2012. A
systematic review on use of Chinese
medicine and acupuncture for treatment
of obesity. Obes Rev, 13: 409-430.
Tang G, Zhang L, Tao J, Wei Z. 2021. Effect
of Nigella sativa in the treatment of
nonalcoholic fatty liver disease: A
systematic review and meta-analysis of
randomized controlled trials. Phytother
Res, 35: 4183-4193.
Yeh GY, Eisenberg DM, Kaptchuk TJ,
Phillips RS. 2003. Systematic review of
herbs and dietary supplements for
glycemic control in diabetes. Diabetes
care, 26: 1277-1294.
Younossi ZM, Marchesini G, Pinto-Cortez H,
Petta S. 2019. Epidemiology of
nonalcoholic fatty liver disease and
nonalcoholic steatohepatitis: Implications
for liver transplantation. Transplantation,
103: 22-27.
)